# A170 DISTRIBUTION OF PHARMACOGENETIC VARIANTS IN PEOPLE SUFFERING FROM ULCERATIVE COLITIS TREATED WITH TARGETED MOLECULAR THERAPIES IN QUEBEC

## TL;DR

This study examines how genetic variants affect treatment response in ulcerative colitis patients in Quebec using targeted molecular therapies.

## Contribution

The study identifies specific pharmacogenetic variants that may influence treatment response to infliximab in ulcerative colitis patients.

## Key findings

- The variant TNFRSF1B-rs3397 was more frequent in UC patients compared to the general Quebec population.
- No other tested pharmacogenetic variants showed significant differences between the UC and populational cohorts.
- The study suggests TNFRSF1B-rs1061622 could be a key variant for understanding infliximab response in UC.

## Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous colonic inflammation. In Canada, ~160,000 people suffer from its symptoms, such as diarrhea, blood in the stool and abdominal pain, which can highly impact their quality of life. For moderate to severe forms of the disease, molecular targeted therapies (MTT) are used to control symptoms and achieve remission. There is a large variability in treatment response to MTT. Indeed, ~20-50% MTT users don’t improve following drug initiation and 50-90% suffer from adverse events. Multiple factors, such as age, sex, tobacco use and pharmacogenetic (PGx) variants, may influence response. However, genetic variants may also impact UC development which may become a confounding factor in treatment response studies.

Therefore, the aim of this study is to validate PGx variants associated with nonresponse by comparing their distribution in UC patients with a populational cohort.

A cohort of 101 people using MTT in UC in Saguenay–Lac-St-Jean was recruited and compared to the populational cohort of CARTaGENE (representing Quebec population, n = 1879). The patients were genotyped for eight PGx variants, distributed across four genes (TNF, TNFAIP3, TNFRSF1A et TNFRSF1B), which were selected as candidates for their previous association with MTT response phenotypes.

The variant TNFRSF1B-rs1061622, previously associated with nonresponse to infliximab (a type of MTT) in a previous study by our team, was comparable between the recruited and populational cohorts. The alternative allele of variant TNFRSF1B-rs3397 was more frequent in the recruited cohort compared to the populational cohort (80,0 vs 67,0 %, p = 0.0001). No other tested variants were differently distributed.

Next steps are to compare these PGx variants with a populational cohort of healthy individuals (exclude individuals suffering from UC in CARTaGENE cohort) to eliminate as many confounding factors as possible. The variant TNFRSF1B-rs1061622 would then be validated and become a great lead to better comprehend treatment response to infliximab in UC. The variant TNFRSF1B-rs3397 needs to be studied more to clarify its potential link to UC development.

CCCFRQS, IRSC, Fondation de ma vie